Exenatide Treatment in Parkinson's Disease

NCT04305002 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ExPD-ESR-18-13512
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The development of a disease-modifying therapy that delays, reverses or stops the symptom progression remains the most important unmet goal in the treatment of Parkinson's disease (PD). Apart from its glucose lowering effect, glucagon-like peptide-1 (GLP-1) receptor stimulation has been investigated in animal models of PD and shown to increase neurogenesis, to arrest and possible reverse nigrostriatal damage, and to protect dopaminergic neurons from neurodegeneration. Exenatide is a synthetic analogue of human GLP-1, resistant to the metabolic processes that degrade it in its naturally occurring form. Results from a recent randomised, double-blind, placebo-controlled trial in PD showed that patients in active treatment for one year were improved compared to the placebo arm with regard to their performance in Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale in the practically defined OFF medication state. The aim of this trial is to investigate the effect of Exenatide, 2 mg, subcutaneous injection, once weekly on disease progression represented by the change in longitudinal Positron emission tomography with 2-deoxy-2-\[fluorine-18\]fluoro- D-glucose (FDG-PET) in individual PD subjects, and to identify an Exenatide-related pattern in FDG-PET that will provide insight into the treatment-effect in the brain. The investigators chose the standard regimen prescribed in Type 2 Diabetes Mellitus (T2DM) and the regimen used in a recent trial in PD. The treatment period will be 18 months, and patients will be randomly assigned to either active treatment or placebo. Patients with PD diagnosis, stable on medication during the last year, and Hoehn and Yahr stage 2 or less will be evaluated for the inclusion.

Conditions

Parkinson Disease

Keywords

Glucagon-Like Peptide 1; Positron-Emission Tomography

Outcome Measures

Primary Outcomes (1)

• FDG-PET network analysis

  21 months

Secondary Outcomes (19)

• The sum score of MDS-UPDRS part 3 in ON and OFF-medication state

  18 and 21 months

• MDS-UPDRS part 2

  9, 18 and 21 months

• MDS-UPDRS part 4

  9, 18 and 21 months

• Hoehn and Yahr

  18 and 21 months

• Accelerometer (intensity of physical activity)

  18 and 21 months

Study Arms (2)

Exenatide

EXPERIMENTAL

Drug: Exenatide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Exenatide DRUG

Injections, 2 mg once weekly for 18 months

Exenatide

Placebo DRUG

Injections, once weekly for 18 months

Placebo

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of clinically probable Parkinson's disease according to the MDS clinical diagnostic criteria for PD
• Males or Females
• Hoehn and Yahr stage ≤ 2 in the ON medication state. This implies that all patients will be mobile without assistance during their best "ON" medication periods.
• Patients are on levodopa treatment.
• No need for extended treatment adjustment, no significant motor fluctuations during the last year.
• All patients will be ≥25 and ≤80 years of age
• Ability to self-administer, or to arrange carer administration of the trial drug.
• Signed informed consent to participate in the trial.

You may not qualify if:

• Atypical or other causes of parkinsonism. Patients with suspected Multiple System Atrophy, Progressive Supranuclear Palsy, drug-induced parkinsonism, vascular parkinsonism, dystonic or essential tremor will not be included in the trial.
• Prior intra-cerebral surgical intervention for Parkinson's disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible.
• Already actively participating in a trial of a device, drug or surgical treatment for Parkinson's disease.
• Previous exposure to Exenatide.
• Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/FDG-PET acquisition.
• Patients with body mass index below 18.5. Exenatide causes weight loss, and individuals with already low BMI will not be eligible.
• Patients with diabetes mellitus type 1.
• Patients with prediabetes (HbA1c at screening 42-47 mmol/mol), or T2DM (known diagnosis, ongoing antidiabetic treatment or HbA1c \> 47 mmol-mol and fasting plasma glucose \> 7.0 mmol/L at screening).
• History of pancreatitis. Baseline serum amylase value should be within the laboratory normal range +/- 20 percent.
• Severe gastrointestinal disease including gastroparesis.
• History of alcoholism.
• History of severe cardiac disease.
• History of pancreas cancer.
• History or suspicion of thyroid cancer. Undiagnosed neck lump, hoarse voice, or difficulty swallowing not attributable to PD.
• Personal or family history of medullary thyroid cancer.

Sponsors & Collaborators

• Center for Neurology, Stockholm: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Academic Specialist Center, Center for Neurology, SLSO

Stockholm, Sweden

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Per Svenningsson

  Academic Specialist Center, Center for Neurology, SLSO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: March 12, 2020
• Study Start: January 21, 2020
• Primary Completion: October 10, 2023
• Study Completion: October 10, 2023
• Last Updated: September 13, 2022

Record last verified: 2022-09

Locations

SE (1)